tbuckley/cabot-search huggingface dataset:
Specialty cancer care and survival in AYA ALL: A U.S. multi-state analysis.
Authors: Lori S. Muffly, Kate Miller, Frances Belda Maguire, Qian Li, Helen M. Parsons, Theresa Keegan
Journal: Journal of Clinical Oncology (2023)

7008 Background: Unlike children with acute lymphoblastic leukemia (ALL) who receive cancer care almost exclusively from pediatric oncologists at specialized cancer centers (SCC; defined here as National Cancer Institute and/or Children’s Oncology Group designated cancer centers), adolescents and young adults (AYAs; 15-39 years) in the United States receive care in a variety of settings. Using state-wide population-based data, we sought to describe the health care delivery settings in which AYAs with ALL receive treatment and determine associations between front-line treatment at an SCC and leukemia-specific and overall survival (LSS/OS). Methods: We used data from the 2004-2018 California (CA), New York (NY), and Texas (TX) state cancer registries to identify front-line treatment setting of AYAs newly diagnosed with ALL. Multivariable logistic regression models evaluated characteristics associated with receiving treatment at an SCC. Cox proportional hazards regression models evaluated the associations with LSS/OS. All models were adjusted for gender, age, sex, race/ethnicity, socioeconomic status, insurance, and diagnosis year. Results: The cohort was comprised of 2283 (CA), 795 (NY), and 955 (TX) AYAs with ALL. Across all states, approximately 70% were ³18 years and 65% were male. Race/ethnicity varied by state: a majority in CA (63%) and TX (64%) were Hispanic, while most in NY were non-Hispanic White (NHW) (50%). Health insurance coverage also varied: most in CA were publicly insured (48%), while most in NY were privately insured (54%); TX had the highest rate of uninsured (18%). Treatment at an SCC occurred in 48.2% (CA), 44.4% (NY), and 19.5% (TX) of AYAs, increasing in CA and NY over time, but remaining unchanged in TX. Among all states, older age and uninsured status were significantly associated with lower odds of treatment at an SCC. In both CA (OR 0.58, 95% CI 0.45-0.74) and TX (OR 0.55, 95% CI 0.35-0.86), Hispanic patients had significantly lower odds of treatment at an SCC than NHW. In NY (OR 0.45, 95% CI 0.31-0.67) and TX (OR 0.49, 95% CI 0.3-0.8), publicly insured AYAs had significantly lower odds of receiving treatment at an SCC than those with private insurance. Front-line treatment at an SCC was significantly associated with both superior LSS (HR 0.73, 95% CI 0.63-0.85) and OS (HR 0.73, 95% CI 0.63-0.85) in CA and superior LSS (HR 0.70, 95% CI 0.51-0.94) and OS (HR 0.61, 95% CI 0.45-0.83) in TX; a non-significant association was seen in NY (LSS: HR 0.86, 95% CI 0.65-1.12; OS: HR 0.83, 95% CI .64-1.08). Conclusions: Only 20-50% of newly diagnosed AYA ALL patients receive front-line treatment at SCCs, with age, race/ethnicity, and insurance type independently influencing AYA ALL care setting. We show that the treatment of ALL at an SCC is associated with superior survival, highlighting the importance of statewide and national policy efforts to improve access and reduce inequities in AYA ALL.
The clinical value of tumor-informed minimal residual disease detection in sarcoma.
Authors: Yiwei Fu, Jingnan Shen, Gang Huang, Changye Zou, Xianbiao Xie, Xiaoliang Shi, Qijie Jian, Jintao Huang, Fei Pang, Junqiang Yin
Journal: Journal of Clinical Oncology (2023)

11510 Background: The high recurrence and metastasis rates lead to poor survival of patients with sarcoma. At present, circulating tumor DNA-based minimal residual disease (MRD) has been studied in varies solid tumors and proved to be valuable in guiding treatment and predicting recurrence, but its application in sarcomas is rarely reported. Methods: Tumor tissue samples were used for whole exome sequencing (WES) and clonal mutations were selected for the customized MRD panel. Blood samples were collected for MRD detection. Experiments were conducted at OrigiMed, a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Results: A total of 84 sarcoma patients including 47 bone tumor (BT), 32 soft-tissue sarcoma (STS), and 5 undifferentiated small round cell sarcoma (USRCS) patients were enrolled. Patients consisted of 49 (58.3%) males and 35 (41.7%) females, with a median age of 23 years old (1-85 years old). Based on WES, we found that 64% (4936/7715) of the mutated genes were unique to each patient, and 70.4% (859/1220) of selected tumor-informed single nucleotide variants (SNV) were variants with unknown significance, suggesting that tumor-informed MRD is superior to panel-based MRD in sarcomas. In this cohort, 78.6% (66/84) of patients successfully constructed MRD panels, including 85.1% (40/47) of BT patients, 75% (24/32) of STS patients, and 40% (2/5) of USRCS patients. The main reason for failure was the scarcity of SNVs detected. Preoperative MRD detection was performed on 6 cases and revealed a positive rate of 100%. MRD detection was performed twice on 2 patients during preoperative neoadjuvant therapy. For the patient with constant allele frequencies detected throughout the treatment course, imaging showed tumor enlargement; While for another patient with a trend of reduction in allelic frequency, imaging showed tumor shrinkage and necrotic tumor tissue was observed in surgery one month later. These two patients had not recurred after surgery at the time of analysis. Post-surgery MRD detection were performed on 27 patients, of which 1 STS and 7 BTs were positive (30%, 8/27). Three of them confirmed recurrence by imaging at 12, 30, and 101 days after detection of positive MRD, respectively. However, there were still no imaging recurrence in the other patients so far, including the 5 remaining patients with positive MRD and 19 patients with negative MRD. Follow-up is still ongoing. Conclusions: MRD tests had been successfully performed in most of the sarcoma patients. Due to the heterogeneity of sarcomas, about 64% of mutated genes of sarcomas are unique individually, which may be more suitable for monitoring with tumor-informed MRD panel. Tumor-informed MRD could be used to predict the efficacy of preoperative neoadjuvant therapy and discover recurrence earlier than imaging in sarcoma.
OATH trial: A phase II clinical trial evaluating the combination of onapristone with anastrozole for women with hormone receptor positive endometrial cancer—Preliminary results.
Authors: Russell J. Schilder, Mark S. Shahin, Mitchell Edelson, Norman G. Rosenblum, Ashley Douglas, Saveri Bhattacharya, Tarek Sahmoud, Elizabeth Burton, Avnish K Bhatia
Journal: Journal of Clinical Oncology (2023)

5601 Background: Endometrial cancer is the most common gynecologic cancer and is primarily treated with chemotherapy. Many endometrial cancers though express hormone receptors and may respond to hormonal therapy, a potentially attractive non-chemotherapy alternative in such a population of women. The aim of OATH is to investigate the potential of dual hormonal blockade through the combination of antiprogesterone and anti-estrogen therapy via the administration of onapristone extended release (ONA) plus anastrozole (ANA), respectively. OATH is an open-label, multicenter, investigator-initiated, non-randomized, phase 2 study to evaluate the safety and efficacy of ONA + ANA in patients (pts) with endometrial cancer (EC). ClinicalTrials.gov Identifier: NCT04719273. Methods: Pts received ONA 50 mg twice daily plus ANA 1 mg once daily and were treated until progressive disease (PD) or unacceptable toxicity. Co-primary endpoints were 4-month progression-free survival (PFS) rate and overall response rate (ORR). A sample size of 25 pts will achieve 80% power to detect an improvement in 4-month PFS estimates from 25% (historical) to 52% and an improvement in response rate from 15% (historical) to 37%, using two-sided exact test at 5% significance level. Secondary endpoints include PFS, disease control rate (DCR), and safety. Results: As of January 20, 2023, 14 pts were enrolled. Median age was 67 years (44-80). ECOG performance status was 0 (36%), and 1 (64%). Number of prior chemotherapy regimens was 0 (1 pt,7%), 1 (9 pts, 64%) and 2 (4 pts, 29%). Seven (50%) pts received radiotherapy and 3 (21%) pts received prior checkpoint inhibitor therapy. Median treatment duration was 4.2 (1.0-19.9) months, and 8 pts remain on treatment. Adverse events were mainly grade 1 and 2. The most common treatment-related adverse events (AEs) and abnormal laboratory values were hot flashes (36%), alanine transferase (ALT) increased (29%), aspartate aminotransferase (AST) increased (29%), nausea (29%), and diarrhea (21%). No treatment-related serious AE, deaths on treatment, or treatment-related drug discontinuations were reported. The 4-month PFS Kaplan-Meier rate was 63.5%. Among 13 pts who had at least one tumor assessment after baseline, the best overall response was: 1 complete response, 1 partial response (response rate: 15.4%), 9 (69%) stable disease, and 2 (15.4%) progressions. Updated results will be presented. Conclusions: Preliminary results of dual hormonal blockade using ONA and ANA in heavily pretreated pts with EC suggest that this combination ONA + ANA has promising activity and is well tolerated. Clinical trial information: NCT04719273 .
FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors.
Authors: Yuxiang Ma, Hongyun Zhao, Jianhua Chen, Zhengbo Song, Yanqiu Zhao, Yubiao Guo, Gang Wu, Wenwei Zhou, Xiaoqing Yu, Fangfang Gao, Ruiguang Zhang, Jian Fang, Xiaoyan Lin, Xiaohong Tian, Yanhua Tu, Juan Yu, GuangLin Liu, Yifan Zhai, Li Zhang
Journal: Journal of Clinical Oncology (2023)

9015 Background: APG-2449 is a novel, orally active FAK inhibitor and an ALK/ROS1 tyrosine kinase inhibitor (TKI) that has shown potent activity in preclinical models. It had been demonstrated that APG-2449 was well tolerated, and preliminary efficacy was observed in pts who were resistant to second-generation ALK/ROS1 + inhibitors (Zhao H et al. J Clin Oncol 2022; 40:9071). We provide updated safety and efficacy results and potential mechanisms of action(s) of this therapy. Methods: After the RP2D was determined as 1,200 mg daily (QD), NSCLC pts were enrolled into 2 dose expansion cohorts. Cohort 1 included pts who were resistant to second-generation ALK/ROS1 + TKIs. Cohort 2 included those who were ALK or ROS1 + TKI naïve. Results: As of December 9, 2022, 130 pts enrolled (median [range] age 53 [21-78] years; 53.8% female) with NSCLC, mesothelioma, or ovarian cancer were treated with APG-2449 at doses ranging from 900 to 1,500 mg. A total of 117 (90%) pts experienced treatment-related adverse events (TRAEs). The most frequent TRAEs included elevated blood creatinine (43.8%), ALT (40.8%), and AST (33.1%) levels, as well as gastrointestinal disorders: nausea (25.4%), vomiting (21.5%), and diarrhea (21.5%). A total of 17 (13.1%) TRAEs were grade ≥ 3. In a subgroup of pts with TKI-naïve NSCLC (n = 33; 31 with efficacy evaluable), the overall response rate (ORR) and the disease control rate (DCR = CR + PR + SD) were 70.6% (12/17) and 88.2% (15/17), respectively, in ROS1 + treatment naïve pts; the ORR and DCR were 78.6% (11/14) and 100% (14/14) in ALK + treatment naïve pts. Of 27 NSCLC pts resistant to second-generation ALK inhibitors, 7 were observed with PR (7/27; 25.9%) during APG-2449 treatment at RP2D. In this subgroup, compared to baseline, pts who experienced PR showed lower phosphorylated FAK (pFAK) levels in peripheral blood mononuclear cells (PBMCs) by Day 28 (24 hours after dosing on D28) than pts who experienced SD. Furthermore, pts with progressive disease showed an increase of PBMC pFAK levels on D28 compared to baseline, indicating that APG-2449 could inhibit FAK phosphorylation. Pts with higher pFAK expression in tumor tissues at baseline tended to achieve better clinical responses than those with lower pFAK expression post APG-2449 treatment. Conclusions: APG-2449 showed a favorable preliminary safety profile and antitumor efficacy in pts with NSCLC. Preliminary efficacy was observed in those whose disease was TKI naïve and resistant to second-generation ALK inhibitors. FAK inhibition could be a novel approach to overcome ALK resistance in pts with NSCLC who are resistant to second-generation ALK inhibitors. Internal study identifier: APG2449XC101. Clinical trial information: NCT03917043 .
Dissecting the relationship between ethnicity and response to checkpoint inhibitors in patients with acral melanoma.
Authors: Firas Y. Kreidieh, Rinata Simien, Ida John, Theresa Rodgers, Noha Abdel-Wahab, Reham Abdel-Wahab, Adi Diab, Kaysia Ludford
Journal: Journal of Clinical Oncology (2023)

e21597 Background: Aral lentiginous melanoma (ALM) constitutes the most common subtype of cutaneous melanoma (CM) among people with pigmented skin, accounting to up to 70% of cases. In a prior study of 44 patients with advanced, unresectable ALM treated with checkpoint inhibitors, we demonstrated differential response to checkpoint inhibitors by ethnicity with Hispanic patients having a higher response to therapy compared to non-Hispanic patients. Accumulating evidence suggests that tumor mutation burden (TMB) can predict the efficacy of immune checkpoint inhibitors (ICI) in solid malignancies, including cutaneous melanoma. ALM however has significantly lower TMB compared to cutaneous melanoma suggesting that there are other mechanisms outside of TMB driving this response. Here, expanding upon our prior work, we will examine outcomes in over 130 patients and report for the first time, the correlation between ethnicity and response to checkpoint inhibitors in the largest dataset to our knowledge of acral melanoma patients. Methods: This was a retrospective analysis of all advanced and metastatic ALM patients treated with anti-CTLA4 (ipilimumab) or anti-PD1 (pembrolizumab or nivolumab) ICI between March 2011 and January 2019 at the University of Texas MD Anderson Cancer Center, Texas. Clinical response, progression free and overall survival outcomes (PFS and OS) and their correlation to ethnicity and TMB will be evaluated. Objective response will be measured using RECIST 1.1. OS and PFS will be estimated using the Kaplan-Meier method, and differences between groups assessed using the log-rank test. Associations between OS and PFS and measures of interest will be determined using Cox proportional hazards regression models. Results: 132 patients with Stages III-IV ALM (III: 27% and IV: 73%) were included in the analysis. Median age was 66.6 years old (15.8-92.5) and 58% were men. 28 (21.2%) self-identified as Hispanic, 101 (76.5%) were non-Hispanic, and 3 (2.3%) did not provide their ethnicity. The best objective response rate (ORR) was 27 (20.4%), with 9 (6.8%) showing complete response (CR) and 18 (13.6%) showing partial response (PR). 48 (36.4%) patients received anti-PD1 based- therapy while 57 (43.2%) received anti-CTLA4 only. We will present immune phenotyping of both adaptive and innate immune arms to investigate further mechanisms of differential response. Conclusions: The data from our prior small retrospective study suggested that non-Hispanic patients with ALM had low response rates to CPI presumably due to low TMB while interestingly, Hispanic patients, despite relatively low TMB have high response rates paralleling those seen in the overall cutaneous melanoma population. This data will provide the rationale to design prospective studies to investigate further how tumor micro-environment varies with ethnicity.
The impact of minority health social vulnerability on population-based cancer incidence.
Authors: Adedayo A. Onitilo, Abdul R. Shour, Ronald Anguzu
Journal: Journal of Clinical Oncology (2023)

e22501 Background: Area-level social determinants of health impact cancer outcomes. However, less is known about how the Minority Health Social Vulnerability Index (MHSVI) affects cancer incidents at the county level. Methods: County-level data from the Agency for Health Care Research and Quality from 2019 for 3,232 counties were analyzed. MHSVI themes: socioeconomic, household composition, minority status/language, housing/transportation, healthcare infrastructure/access, and medical vulnerability were the exposures (continuous). Overall MHSVI were categorized into low (.01/.25), moderate (.26/.74), and high (.75/1) percentiles. The outcome was the total number of cancer incidents (continuous). Covariates include rural-urban regions. Using STATA/MPv.17, unadjusted and adjusted negative binomial regressions with population weighting were performed. P-values of ≤0.05 were considered statistically significant. Results: There were 201,547 total cancer incidents. Adjusted analyses reveal that cancer increased as vulnerability increased especially for household composition (IRR. 1.19, 95% CI: 1.15 – 1.23), healthcare infrastructure/access (IRR. 0.89, 95% CI: 0.87 – 0.91), and housing/transportation (IRR. 0.88, 95% CI: 0.85 – 0.90) themes. Cancer increased in moderate MHSVI areas (IRR. 0.94, 95% CI: 0.92 – 0.96) and high (IRR. 0.86, 95% CI: 0.84 – 0.88) areas compared to low. Conclusions: This study discovered social disparities in cancer incidence. Quantifying the influence of MHSVI on cancer incidents could provide insight into the design/focus of future initiatives aimed at reducing cancer disparities. [Table: see text]
Adverse events during chimeric antigen receptor T-cell (CAR-T) therapy for hematologic malignancies (HM): Real-world, US patient experience.
Authors: Jonathan Kish, Rachael Liu, Srinivasa Vennam, Courtney Lussier, Daniel Pfeffer, Pratibha Nayak
Journal: Journal of Clinical Oncology (2023)

e18891 Background: CAR-T therapy represents the most significant advancement in the treatment of HM in the past 5 years. Life-threatening complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may occur leading to significant morbidity and mortality. We aimed to describes the frequency of CRS and ICANS and the time to onset of each post CAR-T therapy administration in real-world, U.S. patients. Methods: Patients (pts) with HM who received any FDA-approved CAR-T therapy were identified from a U.S. EMR database containing de-identified healthcare data for &gt; 40M patients from &gt; 500 hospitals and 30 healthcare systems (including academic centers). Confirmation of CAR-t treatment was based on ≥1 procedure code for general administration of CAR-T therapy (e.g., XW033C3, introduction of engineered autologous chimeric antigen receptor t-cell immunotherapy into peripheral vein) or a specific approved CAR-T (I.e., XW033K7, introduction of idecabtagene vicleucel immunotherapy into peripheral vein) between 2017 and 2022. Diagnosis of CRS or any ICAN was based ≥1 related ICD-10 diagnosis code (e.g., CRS = D89.83X). Frequency of occurrence of CRS, symptoms of CRS, ICANS symptoms, and severity of CRS or ICANS is described (severity based on validated clinical algorithm). Time to CRS and ICANS was calculated as the interval from CAR-T administration to first reported diagnosis, respectively. Results: 212 pts met the study criteria including 77 b-cell lymphoma, 64 multiple myeloma, 47 follicular lymphoma, 13 mantle cell lymphoma and 11 acute lymphoblastic leukemia pts. The majority were male (54.7%); median age was 60 years. Overall, 100 (47.2%) pts were diagnosed with CRS (any grade) while 82 (38.7%) pts experienced any ICAN symptoms. The top three CRS symptoms were fever (57.5%), hypotension (31.1%) and tachycardia (21.2%). The top three ICANS symptoms were obtundation (18.4%), confusion (12.7%), and delirium (12.7%). Of CRS pts, 25.0% experienced severe symptoms, including renal insufficiency (10.0%), atrial fibrillation (9.0%), ventricular tachycardia (7.0%), and cardiac failure (2.0%). The median time to development of CRS was 2 days (range 0-23 days). Of pts. experiencing ICANS, 72.0% experienced any mild symptom and 53.7% experienced any severe symptom, including obtundation (47.6%), aphasia (13.4%), and seizures (1.2%). The median time to development of ICANS post CAR-T therapy was 6 days (range 0-26 days). Conclusions: Our study is the first real-world, U.S. evaluation of the frequency and time to toxicities associated with CAR-t therapy across multiple hematologic malignancies. While well-described in RCTs these data highlight the need for the continued development of clinical and therapeutic approaches to minimize their impact on the effectiveness of CAR-T.
A study on oligo-progression after durvalumab plus platinum-etoposide for ES-SCLC.
Authors: Kageaki Watanabe, Kazuhito Misawa, Mao Uematsu, Kana Hashimoto, Yukio Hosomi
Journal: Journal of Clinical Oncology (2023)

e20642 Background: Chemotherapy plus immune-checkpoint inhibitor(ICI) therapy is the standard of care for untreated extensive-stage small cell lung cancer(ES-SCLC), but the pattern of progression has not been fully investigated. It is known that a certain percentage of patients with ES-SCLC have Oligo-Progression, and ICI treatment can be continued with the addition of local therapy. This is great significance in the current situation where post-treatment is limited. Methods: We performed a retrospective analysis of patients with ES-SCLC treated with durvalumab plus platinum–etoposide regimen from September 2020 to January 2023 in our institution. Results: Forty patients were included, median age was 68 years (range 45-89), 32 (80%) patients were male and 8 (20%) patients were female, ECOG-PS was 0 or 1 in 25 (63%) patients, 2 or 3 in 15 (38%) patients, 38 (95%) patients had a smoking history, 39 (98%) patients were Stage IV, and the regimens were durvalumab plus cisplatin–etoposide in 15 (38%) patients and durvalumab plus carboplatin–etoposide in 25 (63%) patients. The median PFS was 5.9 months (95% CI: 3.8-8.0) and the median OS was 25.4 months (95% CI: 6.0-44.8). 14(35%) patients were still on treatment. Of the 17 (43%) patients with confirmed RECIST-PD, 4 patients had Oligo-Progression. All of them continued ICI treatment with additional radiation therapy. Two patients are continuing ICI treatment. Two patients with second recurrence, and the time from RECIST-PD to second recurrence was 5 months and 18 months, respectively. Conclusions: Among patients with RECIST-PD after durvalumab plus Platinum–Etoposide for ES-SCLC, Oligo-Progression was observed in 24%, and the strategy of continued ICI treatment in addition to local therapy may be promising.